Process for the treatment of aspartame

ABSTRACT

The invention relates to a process for the treatment of dried aspartame characterized in that, in a first separation step, particles smaller than 50 μm are removed, with the aid of a stream of air, from aspartame having a particle size distribution with which more than 5 wt. % of the aspartame has a particle size of less than 20 μm and more than 10 wt. % of the aspartame has a particle size of more than 400 μm, and that in a second separation step the product resulting from the first step is subjected to a screening step using a screen that separates at a value between 150 and 250 μm, after which the fraction of the smaller particles thus obtained is recovered as a first product and the fraction of the larger particles is recovered as a second product or is optionally subjected to a further separation step using a screen that separates at a value between 400 and 1000 μm, the fraction of smaller particles thus obtained being recovered as the second product. Aspartame having a particle size distribution in which at least 94% of the particles are larger than 20 μm and smaller than 250 μm appears to present exceptionally good properties as regards processability and dissolution rate.

This patent application is a Continuation-In-Part of U.S. patentapplication Ser. No. 08/074,446, filed Jun. 10, 1993, now U.S. Pat. No.5,411,747 the entire contents of which are hereby incorporated byreference and relied upon.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to a process for the treatment of driedaspartame, and to aspartame thus recovered.

2. Description of the Related Art

Aspartame is a sweetener that is often used in low-calorie lemonades,sugar-free chewing gum and low-calorie sweeteners. Aspartame is oftensold as a "powder" consisting of particles smaller than 1 mm. Thispowder usually has a wide particle size distribution: there is asignificant fraction of particles with sizes between 0 and 20 μm, 20-50μm, etc. This type of product appears to be (1) relatively poorlysoluble, (2) electrostatically chargeable, (3) non-free-flowing, (4) thecause of dust problems, (5) difficult to dose and (6) poorly dispersiblein water.

In order to prevent some of these problems, aspartame is sometimes soldof which 90 wt. % of the particles are between, say, 250 and 750 μm.This aspartame, however, has a relatively low dissolution rate. Inaddition, it presents the drawback that a special treatment, for examplea granulation step, is required afterwards to process undesired material(aspartame with particle sizes outside this range).

The present invention provides a process for the treatment of driedaspartame with which a product of a very high quality and gooddissolution rate is obtained and with which only very little materialneed be reprocessed.

SUMMARY OF THE INVENTION

The present invention discloses aspartame in particulate form having aparticle size distribution within a range of 20 μm to 250 μm, wherein atleast 94 wt. % of the aspartame particles are within said range.

The present invention also discloses such aspartame, wherein at least 90wt. % of the particles are larger than 30 μm and such aspartame, whereinat least 90 wt % of the particles are larger than 50 μm.

The present invention further discloses such aspartame, wherein at least97 wt. % of the particles are larger than 30 μm and such aspartame,wherein at least 97 wt. % of the particles are larger than 40 μm.

The present invention also discloses such aspartame, wherein at least 97wt. % of the particles are less than 220 μm and such aspartame, whereinat least 97 wt. % of the particles are less than 205 μm.

The present invention also discloses a tablet obtained by tabletingaspartame particles, wherein at least 94 wt. % of the particles are in aparticle size distribution range of 20 μm to 250 μm.

The present invention further discloses such a tablet, wherein at least90 wt. % of the aspartame particles are larger than 30 μm and such atablet, wherein at least 90 wt. % of the aspartame particles are largerthan 50 μm.

The present invention further discloses such a tablet, wherein at least97 wt. % of the aspartame particles are larger than 30 μm and such atablet, wherein at least 97 wt. % of the aspartame particles are largerthan 40 μm.

The present invention further discloses such a tablet, wherein at least97 wt. % of the aspartame particles are less than 220 μm and such atablet, wherein at least 97 wt. % of the aspartame particles are lessthan 205 μm.

The present invention also discloses a tablet obtained by preparingdried aspartame, wherein in a first separation step, particles smallerthan 50 μm are removed, with the aid of a stream of air, from aspartamehaving a particle size distribution with which more than 5 wt. % of theaspartame has a particle size of less than 20 μm and more than 10 wt. %of the aspartame has a particle size of more than 400 μm and that in asecond separation step, the product resulting from the first step issubjected to a screening step using a screen that separates at a valuebetween 150 and 250 μm, after which the fraction of the smallerparticles thus obtained is recovered as a first product dried aspartameand the fraction of the larger particles is recovered as a secondproduct dried aspartame or is optionally subjected to a furtherseparation step using a screen that separates at a value between 400 and1000 μm, the fraction of smaller particles thus obtained being recoveredas a second product dried aspartame and preparing a tablet comprisingthe first product dried aspartame.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The process for the treatment of dried aspartame is characterized inthat, in a first separation step, particles smaller than 50 μm areremoved for the most part, with the aid of a stream of air, fromaspartame having a particle size distribution with which more than 5 wt.% of the aspartame has a particle size of less than 20 μm and more than10 wt. % of the aspartame has a particle size of more than 400 μm and,in a second separation step, the product resulting from the first stepis subjected to a screening step using a screen that separates at avalue between 150 and 250 μm, after which the fraction of the smallerparticles thus obtained is recovered as a first product dried aspartameand the fraction of the larger particles is recovered as a secondproduct dried aspartame or is optionally subjected to a furtherseparation step using a screen that separates at a value between 400 and1000 μm, the fraction of smaller particles thus obtained being recoveredas a second product dried aspartame.

In the first step, particles smaller than 40 μm, in particular smallerthan 30 μm, more in particular particles smaller than 20 μm, arepreferably separated (hereinafter to be referred to as very fineaspartame), the fractions of particles larger than 40 μm, larger than 30μm and larger than 20 μm, respectively, being the product resulting fromthe first step.

The very fine aspartame is preferably returned to the process. Thisaspartame may, for example, be dissolved and recrystallized. It is alsopossible, and preferable, to mix this aspartame with aspartame slurryfrom a crystallizer or centrifuge for a granulation and drying step.

A classifier and a stream of air are used to separate this very fineaspartame. As a rule, more than 1 kg of air per kg of aspartame is usedas the stream of air. Preferably, use is made of between 2 and 50 kg ofair, in particular of between 5 and 20 kg per kg of aspartame. Verysuitable is, for example, a "Sweco Turbo-Screen" (hereinafter also to bereferred to as TS) manufactured by Sweco. It is not possible to effectgood separation in practice using an ordinary screen, without anadditional driving force of a stream of air.

In addition, the classifier medium (usually a very fine screen or aplate with very small holes) is preferably continuously cleaned. Thiscan be done, for example, by vibrating the screen or plate or bycountercurrently blowing air through the screen or plate in places.

In order to separate very fine aspartame, the use of a fluidized bed isalso very suitable. As a rule, the rate of fluidization will be chosenbetween 5 and 25 cm/sec. The thickness of the layer in the fluid bed mayvary within a wide range without affecting the separation essentially.

For the process according to the invention, it appears to be veryimportant to separate very fine aspartame in a first separation step.This ensures that the next separation step, using a screen thatseparates at 150-250 μm, takes place without problems in a veryefficient manner. When a screening step at for example 200 μm wascarried out as the first separation step, the screening apparatus becamefouled/blocked and it proved difficult to dose the aspartame.

The product resulting from the first separation step is subjected to asecond separation step using a screen that separates at a value between150 and 250 μm. Preferably, the screen separates at a value between 170and 220 μm, in particular at a value between 180 and 205 μm.

The fraction of the larger particles resulting from the secondseparation step is either directly recovered as a second product or itis subjected to a further separation step to remove relatively coarsematerial. Use can be made of a screen that separates at a value between400 and 1000 μm, depending on the desired application of the aspartameproduct. If only the coarsest material is to be removed, a screen thatseparates at a value between 900 and 1000 μm is very suitable. Such ascreening step may optionally also take place before the secondseparation step, but that is not preferable because then all of theaspartame (with the exception of the very fine aspartame) is subjectedto this screening step, which means that a relatively large screen isrequired, which is less attractive from an economic point of view.

The separated coarse material can be ground and returned to thebeginning of the treatment section for the use of the process accordingto the invention.

In this manner several fractions of aspartame are obtained, the fractionrecovered as the first product in particular having very goodproperties. In particular the combination of a high dissolution rate,good flow properties (free flowing), good dispersibility, little dustformation and the virtual absence of electrostatic charging is unique.In addition, this aspartame appears to be extremely suitable for use intablets, powders and chewing gum in particular, because the absence oflarger particles means that a good distribution of aspartame throughoutthe product is obtained.

In commercial scale tableting of aspartame, using standard equipment(direct compression type equipment in general is considered to be themost preferred equipment for tableting) and "state of the art" aspartameproducts as of the priority date of U.S. patent application Ser. No.08/074,446, U.S. Pat. No. 5,411,747 many problems occurred, whatevertype of excipient and/or tableting agent was added in the process. Themain problems were that the tablets tended to "adhere"/"stick" to thepunches or dies of the tableting machine (which according to our presentunderstanding may be attributed to the presence of microcrystallineproduct in the aspartame) and that the tableting equipment could not berun/operated smoothly.

The permanent presence of one or more operators, who needed to take manycorrective actions during the processing of tablets, was required torun/operate the tableting equipment properly. The equipment often had tobe stopped or operating conditions had to be adjusted (e.g., by loweringthe rotation speed of the equipment), and feed to the tableting machinehad to be kept in motion by tapping/knocking from the outside. Itusually turned out to be impossible to continue production of tabletsuntil all of the starting material had been processed; final partsthereof usually could not be pressed into the tableting machine.

This conventional tableting process resulted in relatively lowproduction capacity of tablets, and in a high rejection percentage oftablets produced (poor quality). Moreover, the tablets made showed abroad range of distribution of weight and strength, and were not veryuniform. In addition, production of tablets caused much noise, becausethe machinery could not operate smoothly and tapping/knocking wasnecessary. And last, but not least, the outer appearance of the tabletsproduced was relatively poor, especially in such cases where one wantedto "imprint" lines, signs, circles or figures, etc., at the surface ofthe tablets. In those cases, the problems of "adhering/sticking" to thepunches and dies were even larger.

The above-described problems in the tableting process have now beenovercome by using the aspartame made according to the process disclosedherein. This has been demonstrated in production scale experiments usingtableting equipment which previously had been used (experiencing theproblems mentioned above) for various years with "state of the art"aspartame products. In these experiments performed on a Kilian highspeed rotating tableting machine, having 51×6 punches, and a maximumcapacity of 1.8×10⁶ tablets per hour at a maximum rotation speed of 49rpm, aspartame was tableted together with "tablettose"(commercially-sold free flowing lactose product, for tableting purposes,from Meggler) as is used in the conventional production runs.

Though it is known in principle that relatively large particles ofaspartame can be tableted, tablets made from such course productsusually tend to be undesirable, i.e., commercially unattractive, due tothe poor dissolution rate characteristics of the products obtained.Dissolution rate properties as such would be better if relatively fineaspartame particles would be used, however, such product is very poor inflowing properties, and therefore not very suitable for tableting. Itnow, surprisingly, has been found that the aspartame product of thepresent invention is most suitable for tableting purposes, and resultsin tablets having good dissolution properties. Most surprisingly, italso has been found that the outer appearance of the tablets obtained ismuch improved as compared with the known tablets, and, especially thatlines, signs, circles or figures, etc., could be imprinted at thesurface of the tablets during the tableting process in a very exact way.

It clearly has been demonstrated that direct compression tableting ofaspartame, obtained according to the method of the present application,is very favorable. The tablets obtained are very homogeneous anduniform, both in weight and strength; the tableting machinery can beoperated without attendance for many hours, and without problems ofundesired noise levels, etc.; no tapping/knocking is necessary, and noadhering/sticking of product to the punches and dies occurs; therejection percentage of tablets made in this way is extremely low; andfinally, production can be continued undisturbed until all of thestarting material has been converted into tablets.

The aspartame used in the production of these tablets is prepared fromthe above-described first product dried aspartame and is characterizedby a narrow particle size distribution in which 97 wt. % of theparticles are larger than 20 μm, preferably larger than 30 μm, inparticular larger than 40 μm. In addition, 97 wt. % of the particles aresmaller than 250 μm, preferably smaller than 220 μm, in particularsmaller than 205 μm. In addition, 90 wt. % of the particles arepreferably larger than 30 μm, in particular larger than 50 μm. Thedifferent values preferred for the upper and lower limits can becombined with one another in different manners for products that meetspecific economic or technical requirements.

The second product dried aspartame is a granular type of aspartame thathas a good bulk density and is easily processable but dissolves lessquickly than the first product.

As starting material for the process according to the invention, use ispreferably made of dry aspartame with a moisture content of less than 6wt. % in particular with a moisture content of 1-4 wt. %. The aspartameis usually recovered through crystallization from an aqueous solution.The slurry finally obtained is filtered off with the aid of for examplea centrifuge and the wet cake (containing about 25-60 wt. % water) isdried and optionally granulated. In the granulation step or steps,aspartame may already be formed that has a particle size distributionthat makes it suitable for use in the process according to theinvention. If, however, a relatively large amount of coarse material ispresent, for example, if more than 20 wt. % has a particle size of morethan 1 mm, then it is preferable to grind the material first.

The starting material usually has a wide particle size distribution,which is the result of the mechanical forces exerted during thegranulation, reduction and drying steps. As a rule, the aspartame hassuch a distribution that more than 5 wt. % of the aspartame has aparticle size of less than 20 μm and that more than 10 wt. % has aparticle size of more than 400 μm.

Although it is common to speak of separation at a particular value inthe case of, for example, screening, it is of course true that aroundthat value a portion of the material having a smaller particle size willnot pass through the screen and a portion of the larger material will,depending on the efficiency of the screen. This is because the holes ofa screen are not all as large as one another and the particles are notideally round.

The invention will be elucidated with reference to the followingnon-limiting examples.

EXAMPLE 1

Aspartame obtained through centrifugation, granulation, drying andgrinding had the following characteristics:

d₁₀ :40 μm

d₅₀ :180 μm

d₉₀ :820 μm

moisture:2.8 wt. %

This aspartame was subjected to the following steps:

1) treatment in a Sweco TS 18, using a plate that separates at 50 μm anda stream of air of 10 kg of air per kg of aspartame. The fine materialwas returned to the granulation section where it was dispersed in thecentrifuged aspartame slurry;

2) the resulting product was passed through a 200-μm screen. Thefraction of the smaller particles was recovered as product 1;

3) the material consisting of the larger particles was passed through a900-μm screen. The coarse material was returned to the grinding step;the desired fraction was recovered as product 2.

14% very fine and 5% coarse aspartame were separated. 40% product 1 and40% product 2 were recovered and there was 1% loss.

The properties of the products are shown in Table 1.

                  TABLE 1                                                         ______________________________________                                                   Product 1                                                                             Product 2                                                  ______________________________________                                        d.sub.3      32 μm  180 μm                                              d.sub.10     55 μm  230 μm                                              d.sub.50     95 μm  400 μm                                              d.sub.90     180 μm 700 μm                                              d.sub.97     200 μm 900 μm                                              ______________________________________                                         Further properties of product 1 were:                                         settling angle: 24°-                                                   bulk density: 410 kg/m.sup.3 -                                                outflow time*: 9 sec                                                          dissolution rate**: 4 min                                                     *the amount of time that it took for 20 cm.sup.3 of product to flow out o     a funnel with an outflow aperture with a diameter of 9 mm was measured;       **0.4 g of aspartame in 1 liter of water at 20° C., using a            magnetic stirrer and a stirring rod whose diameter was half that of the       vessel; 200 rpm in a 2liter beaker.                                      

COMPARATIVE EXAMPLE 1

Aspartame as described in Example 1 was passed through a 200-μm screen.The screen became blocked several times. The cleaning of the screencaused a 5% loss of product. The screened product presented thefollowing properties:

                  TABLE 2                                                         ______________________________________                                                comparative product                                                   ______________________________________                                        d.sub.10   20                                                                 d.sub.50   70                                                                 d.sub.90  160                                                                 d.sub.99  200                                                                 ______________________________________                                         settling angle: 34°-                                                   bulk density: 385 kg/m.sup.3 -                                                outflow time: ∞-                                                        dissolution rate: 8 min                                                  

EXAMPLE 2 AND COMPARATIVE EXAMPLES 2 AND 3

The advantages of use of aspartame according to the present inventionfor the preparation of tablets can be seen by comparing the results ofthe following example using Holland Sweetener test product according tothe present invention (product A), and comparative examples usingNutraSweet® powder product (product B) or Holland Sweetener Companypowder product (product C). Example 2 and Comparative Examples 2 and 3were performed under comparable conditions (Kilian; high speed rotatingtableting machine; 51×6 punches; maximum capacity of 1.8×10⁶ tablets perhour at 49 rpm maximum). The composition of the starting mixture was ineach case 35 wt % of aspartame and 65 wt. % of tablettose (Meggler),with minor amounts of other standard ingredients for assisting thetableting process, identical in all cases.

Only in the case of use of product A (aspartame particles obtainedaccording to the method of the present invention) was it possible to runthe equipment smoothly at maximum capacity for many hours. In thecomparative examples, adjustment of rotation speed to about 40 rpm wasnecessary, and the operation required much attention. The outerappearance of tablets made from product A was much better than of thosemade from products B and C.

Relevant data for starting materials and tablets produced are shown inTable 3. The data for the aspartame (APM) starting material (in thetableting step) also show various values which are important inestimating the flow properties of said product. These data have beendetermined according to standard methods known to those skilled in theart. The combined criteria for flow properties are usually presented inthe form of the "Carr index", a classification system first presented byRalph L. Carr, Jr., in "Chemical Engineering", 1965 pages 163-168, andincorporated herewith by reference. This reference also shows how thevarious data can be determined. A total "Carr point score" above 70indicates that the product will flow fairly well without aid (thoughoccasionally some vibration might be needed); a "Carr point score" inthe range of 40 to 59 means that flowability is poor and thatagitation/vibration is necessary for keeping the product in motion whenflowing; a "Carr point score" of 20 to 39 indicates that flowability andperformance are very poor, and more positive agitation is required inmoving the product.

From the results shown in the Table 3, it is clear that tabletscomprising aspartame according to the present invention can be producedat a higher production rate and more smoothly, with less spread ofresults in average tablet weight, aspartame content and strength oftablets, as compared to tablets prepared from conventional aspartameparticles.

                  TABLE 3                                                         ______________________________________                                        TABLETING OF ASPARTAME WITH TABLETTOSE                                                      Present                                                                       Invention                                                                     Product                                                                              Comparative Examples                                     Item                A        Product B                                                                             Product C                                ______________________________________                                             DATA STARTING                                                                 MATERIAL APM                                                             1.   particle size                                                                 % < 20 μm   n.d.     n.d.    11.69%                                        % < 50 μm   1.81%    99%     n.d.                                          % < 75 μm   n.d.     n.d.    54.45%                                        % > 200 μm  0.57%    0%      4.69%                                         d.sub.50       130 μm        70 μm                                      d.sub.90       186 μm                                                                              21 μm                                                                              175 μm                                     d.sub.95       194 μm                                                                              37 μm                                                                              199 μm                                2.   angle of repose                                                                              31.6°                                                                           50.8°                                                                          48.3°                                  CARR POINTS    21.8     12.1    13.3                                     3.   Free bulk density                                                                            445      215 kg/m.sup.3                                                                        267 kg/m.sup.3                                               kg/m.sup.3                                                     Tapped bulk density                                                                          538      355 kg/m.sup.3                                                                        374 kg/m.sup.3                                               kg/m.sup.3                                                     Compressibility                                                                              16.4%    39.6%   28.6%                                         CARR POINTS    19.3     3.3     12.1                                     4.   Angle of rupture                                                                             35.1°                                                                           56.8°                                                                          46.0°                                  CARR POINTS    21.6     14.3    18.0                                     5.   Cohesion       19.1%    36.6%   10.4%                                         CARR POINTS    11.8     8.4     13.4                                     6.   Total points Carr                                                                            74.5     38.1    56.8                                          DATA ON PRO-                                                                  DUCTION OF                                                                    TABLETS                                                                       COMPRISING APM                                                           7.   max. possible speed                                                                          49 rpm   <40 rpm <40 rpm                                       of rotation for                                                                              (= limit                                                       smooth production                                                                            of equip-                                                                     ment)                                                     8.   outer appearance                                                                             ++       +/-     +/-                                      9.   attention needed                                                                             no       yes     yes                                           during production                                                        10.  average tablet 50 mg    47 mg   48 mg                                         weight                                                                        standard deviation                                                                           1.9%     4.3%    3.0%                                     11.  average APM content                                                                          17.64 mg 16.3 mg n.d.                                          standard deviation                                                                           2.2%     3.8%    n.d.                                     12.  average strength of                                                                          20.5 N   21.9 N  10.5 N                                        tablet                                                                        standard deviation                                                                           11%      21%     26%                                      ______________________________________                                    

While the present invention has been described in connection with whatis presently considered to be the most practical and preferredembodiment, it is to be understood that the invention is not to belimited to the disclosed embodiment, but on the contrary is intended tocover various modifications and equivalent arrangements included withinthe spirit and scope of the appended claims.

Thus, it is to be understood that variations in the present inventioncan be made without departing from the novel aspects of this inventionas defined in the claims.

What is claimed is:
 1. A tablet comprising aspartame, obtained by directcompression tableting aspartame particles, wherein at least 94 wt. % ofsaid aspartame particles are in a particle size distribution range of 20μm to 250 μm.
 2. The tablet of claim 1, wherein at least 90 wt. % ofsaid aspartame particles are larger than 30 μm.
 3. The tablet of claim1, wherein at least 90 wt. % of said aspartame particles are larger than50 μm.
 4. The tablet of claim 1, wherein at least 97 wt. % of saidaspartame particles are larger than 30 μm.
 5. The tablet of claim 1,wherein at least 97 wt. % of said aspartame particles are larger than 40μm.
 6. The tablet of claim 1, wherein at least 97 wt. % of saidaspartame particles are less than 220 μm.
 7. The tablet of claim 1,wherein at least 97 wt. % of said aspartame particles are less than 205μm.
 8. The tablet of claim 1, further comprising excipients or tabletingagents.
 9. The tablet of claim 1, further comprising excipients andtableting agents.
 10. A tablet obtained bya) preparing dried aspartame,whereinin a first separation step, particles smaller than 20 μm areremoved, with the aid of a stream of air, from aspartame having aparticle size distribution with which more than 5 wt. % of the aspartamehas a particle size of less than 20 μm and more than 10 wt. % of theaspartame has a particle size of more than 400 μm and that, in a secondseparation step, the product resulting from the first step is subjectedto a screening step using a screen that separates at a value between 150and 250 μm, after which the fraction of the smaller particles thusobtained is recovered as a first product dried aspartame and thefraction of the larger particles is recovered as a second product driedaspartame or is optionally subjected to a further separation step usinga screen that separates at a value between 400 and 1000 μm, the fractionof smaller particles thus obtained being recovered as a second productdried aspartame and b) preparing a tablet comprising said first productdried aspartame.
 11. The tablet of claim 10, further comprisingexcipients or tableting agents.
 12. The tablet of claim 10, furthercomprising excipients and tableting agents.
 13. A tablet obtainedaccording to claim 10, wherein in said first separation step, particlessmaller than 30 μm are removed.
 14. A tablet obtained according to claim10, wherein in said first separation step, particles smaller than 40 μmare removed.
 15. A tablet obtained according to claim 10, wherein insaid first separation step, particles smaller than 50 μm are removed.